Patients suffering from diabetes, in particular type 1 diabetes, require insulin replacement therapy to compensate for the loss of their pancreatic islet cells. The goal in this therapy is to maintain glucose levels in the normal range by replicating the physiological pattern of insulin secretion of the healthy pancreas, thereby avoiding short-term complications (i.e., hypoglycaemia or hyperglycaemia with ketosis and osmotic diuresis) as well as long-term vascular complications (e.g., renal failure, blindness, myocardial infarction, stroke, limb amputation). At present, the vast majority of type 1 diabetic patients self-administer insulin either by a subcutaneous bolus injection using a hypodermic needle (e.g., syringe, insulin pen) or by a subcutaneous infusion using an indwelling catheter connected to an insulin pump (insulin pump therapy). In addition, to guide adjustments in insulin dosage, food consumption and physical activity, people with type 1 diabetes self-monitor blood glucose levels by typically measuring glucose in blood obtained using finger-pricking. In the treatment of diabetes using an infusion apparatus, such as an insulin pump, insulin is usually administered at a high rate before meals (bolus insulin delivery) and at a low rate after meals and during night (basal insulin delivery). Most current insulin pumps deliver the basal insulin as small pulses with relatively long time intervals between pulses (up to several minutes). The bolus insulin, however, is usually delivered as macro-pulses with a high repetition frequency of the pulses (pulse intervals equal to or smaller than four seconds). Thus, the length of a bolus delivery period (bolus duration) usually depends on the bolus size (e.g. total volume or total mass) chosen by the patient and on the repetition frequency and magnitude of the macro-pulses employed in the insulin pump. For example, a typical bolus amount may be ten to fifteen units of insulin. Thus, when insulin pump models with high pulse frequency and/or large pulse sizes are used, then a typical bolus amount of insulin is administered during a time span of one minute or less. However, with insulin pump models featuring smaller pulse sizes and/or lower pulse frequency, typical bolus amounts of insulin are delivered over a longer time span (e.g., 10 min), in order to prevent burning sensation at the infusion site, to delimit the power consumption or the like.
In the treatment of diabetes using an insulin pump, the insulin is infused into the tissue through an indwelling catheter (e.g., Teflon cannula or steel needle). A general recommendation of drug and device manufacturers is to change the indwelling catheter and the infusion site every 2-3 days in order to avoid infection and lipohyperthrophy at the infusion site as well as deterioration in control of the blood glucose concentration due to reduced insulin absorption. It has been shown that there is considerable inter- and intra-individual variability in the length of use of the indwelling catheters and infusion sites and that in a large group of diabetic patients the duration of use of catheter and infusion site can be safely prolonged beyond the recommended 2-3 day period. Thus, in order to improve the therapy with insulin pumps and to reduce costs associated with this therapy, it would be desirable to individually determine the longest possible duration of use of a particular infusion site and to alert the patient to change the indwelling catheter and the infusion site when the maximum usage duration is reached.
Furthermore, it has been previously shown that the insulin absorption rate following subcutaneous administration of a bolus amount of insulin is associated with a large inter- and intra-individual variability, which may arise from various exogenous factors including injection technique, infusion pressure and bolus length applied in the insulin pump, as well as endogenous factors including tissue geometry, convective and diffusive transport of the insulin in the tissue, and tissue blood flow. In addition, it has been observed that, when a bolus amount of insulin is injected or infused into the subcutaneous tissue, the subcutaneous insulin absorption from the administration site into the blood is much slower than the insulin secretion from the healthy pancreas into the blood.
These and other limitations may make it difficult for type 1 diabetic patients to achieve physiologic insulin replacement patterns and, consequently, glycemic control is frequently insufficient in these patients. Therefore, rates of co-morbidity and mortality continue to be greatly elevated in type 1 diabetic patients.